Primary Human Immunodeficiency Virus (HIV) infection is the period of high-level viremia associated with initial acquisition of HIV, which is followed by chronic HIV infection. Clinical studies exploring the optimal management of patients with both primary and chronic HIV infection generally report short-term surrogate markers such as CD4 cell count or HIV plasma RNA rather than clinical outcomes. Disease simulation models are particularly useful for incorporating clinical trial results to assist in making long-term management decisions. A major strength of decision modeling in HIV is the ability to include up-to-date data on treatment efficacy into models to estimate outcomes such as life expectancy, quality of life, and costs of care. Using a detailed simulation model of HIV infection, the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) group has focused on late-stage HIV clinical management. Using the CEPAC model as the basis for this research, this proposal will accomplish four specific aims: 1) to incorporate data on primary HIV infection and viral replicative fitness into the CEPAC model. 2) To project the impact of early highly active antiretroviral therapy for primary HIV infection on life expectancy, quality of life and costs of care using both a pilot simulation model and the CEPAC model. 3) To estimate at what prevalence of primary HIV infection it would be beneficial to screen episodic-care patients, who present with a viral syndrome, for primary HIV infection using an HIV plasma RNA test. 4) To assess the impact of changes in antiretroviral-induced diminished HIV replicative capacity on optimal treatment strategies for chronic infection. This work will provide insight into the ideal antiretroviral management of both primary and chronic HIV infection, a major goal of the Office of AIDS Research. A diverse team of mentors with expertise in infectious disease, clinical epidemiology, and disease modeling will provide Dr. Rochelle Walensky with a firm basis for career development as an independent, patient-oriented clinical researcher at the interface of these critical areas.